Curr Opin Investig Drugs, 2004 Feb, 5(2), 146 - 53 Fatty acid biosynthesis as a target for novel antibacterials; Heath RJ et al.; The bacterial fatty acid synthesis pathway has significant potential as a target for the development of novel antibacterials . The pathway has been extensively studied in Escherichia coli, the crystal structures of the compounds involved are known and homologous genes are readily identified in the genomes of important pathogens . The currently used drugs triclosan and isoniazid are known to target one step in the pathway . Other experimental compounds such as thiolactomycin and cerulenin effectively inhibit other steps . These known pathway inhibitors are reviewed and the areas for potential future developments are explored. Nucleosides Nucleotides Nucleic Acids, 2004, 23(1-2), 161 - 70 Synthesis and biological activity of 5-fluorotubercidin; Wang X et al.; The electrophilic fluorination of 4-chloropyrrolo{2,3-d}pyrimidine (1) was studied culminating a 59% conversion of compound 1 to 4-chloro-5-fluoropyrrolo{2,3-d}pyrimidine (2) using Selectfluor . This transformation proceeded via the 4-chloro-5,6-dihydro-5-fluoro-6-hydroxypyrrolo{2,3-d}pyrimidine (3) in a 9:1 trans:cis ratio . The trans isomer of compound 3 was studied by 1H NMR and 19F NMR, and the 5-H tautomer (4) was observed as another intermediate . A modified Vorbruggen procedure of compound 2 and tetra-O-acetylribose gave 4-chloro-5-fluoro-7-(2,3,5,-tri-O-benzoyl-beta-D-ribofuranosyl)pyrrolo{2,3-d}pyrimidine (6) in a 65% yield . Treatment of compound 6 with ammonia (l) in dioxane gave 5-fluorotubercidin (7) . No antibacterial activity was observed . An MTT assay (Promega) against Huh-7 liver cells, normal mouse spleen cells stimulated with Con A (a T-cell mitogen), and normal mouse spleen stimulated with LPS (a B-cell mitogen) showed no significant toxicity . Increased activity of 7 over tubercidin was observed against L-1210 cells and toxicity in fibroblast cells was reduced. Amino Acids, 2004 Mar, 26(2), 139 - 46 Epub 2003 Dec 31. Synthesis of novel 3-pyridinecarbonitriles with amino acid function and their fluorescence properties; Girgis AS et al.; A variety of N-{(4,6-diaryl-3-pyridinecarbonitrile)-2-yl} amino acid esters 2-4 were synthesized through the reaction of 2-bromo-3-pyridinecarbonitriles 1 with the appropriate alpha-amino acid ester hydrochloride in refluxing dioxane in the presence of triethylamine as dehydrohalogenating agent . Similarly, N'-glycylglycine analogues 5 were obtained through the reaction of 1 with the dipeptide ester . On the other hand, attempts were made towards the construction of amino acid derivatives 7 through the reaction of 1 with aqueous solution alpha-amino acids 6 in refluxing pyridine, but were unsuccessful, and instead the unexpected 2-amino-3-pyridinecarbonitriles 8 were isolated . The fluorescence properties of the newly synthesized pyridines 2-5 were evaluated . Some of the prepared compounds show considerable antibacterial activity. Nat Rev Microbiol, 2003 Oct, 1(1), 65 - 70 Where will new antibiotics come from? Walsh C. There is a constant need for new antibacterial drugs owing to the inevitable development of resistance that follows the introduction of antibiotics to the clinic . When a new class of antibiotic is introduced, it is effective at first, but will eventually select for survival of the small fraction of bacterial populations that have an intrinsic or acquired resistance mechanism . Pathogens that are resistant to multiple drugs emerge around the globe, so how robust are antibiotic discovery processes? Clin Ther, 2004 Feb, 26(2), 191 - 6 Topical antibacterial therapy for mycobacterial keratitis: potential for surgical prophylaxis and treatment; Abshire R et al.; BACKGROUND: Mycobacterium chelonae and Mycobacterium fortuitum are the 2 most commonly implicated species of nontuberculous mycobacteria in cases of bacterial keratitis . OBJECTIVES: This article summarizes available data on the in vitro antibacterial activity against M chelonae or M fortuitum of 2 agents-amikacin and clarithromycin-that have been used in the treatment of bacterial keratitis . In addition, the article reviews the in vitro activity of 5 commercially available topical ocular fluoro-quinolones (in order of availability, ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin) that may have potential in the surgical prophylaxis and treatment of keratitis caused by M chelonae or M fortuitum . METHODS: A search of the English-language literature indexed on the MEDLINE, Life Sciences, EMBASE, BIOSIS, and Pharmaprojects databases from 1966 to October 7, 2003, was conducted using the terms Mycobacterium chelonae, Mycobacterium fortuitum, bacterial keratitis, topical antibiotic therapy, ocular infection-mycobacteria, and LASIK infections . Data on the minimum concentrations at which 90% of isolates were inhibited (MIC(90)s) were reviewed and compared . RESULTS: In the literature reviewed, the MIC(90) against M fortuitum was from 1 to 16 microg/mL for amikacin, from </=2 to >/=8 microg/mL for clarithromycin, from 0.1 to 1 microg/mL for ciprofloxacin, from 0.5 to 3.13 microg/mL for ofloxacin, and </=2 microg/mL for levofloxacin . The results were similar against M chelonae . The fourth-generation fluoroquinolones-gatifloxacin and moxifloxacin-had similar MIC(90)s against M fortuitum (both, 0.2 to 1 microg/mL); however, moxifloxacin had greater activity than gatifloxacin against M chelonae (minimum inhibitory concentration range: moxifloxacin, </=1 to 1.6 microg/mL; gatifloxacin, 3.2 to 6.25 microg/mL) . CONCLUSIONS: Topical fluoroquinolones may be beneficial for ocular surgical prophylaxis and for the treatment of keratitis caused by M chelonae or M fortuitum . Based on their reported MIC(90)s, none of the antibacterials reviewed had greater in vitro activity than moxifloxacin . In addition, moxifloxacin had greater in vitro activity than gatifloxacin against M chelonae, one of the predominant nontuberculous mycobacterial species involved in bacterial keratitis . Pending the conduct of controlled clinical studies, these findings suggest that moxifloxacin may have utility in the prevention and treatment of atypical mycobacterial keratitis. Arch Pharm (Weinheim), 2004 Mar, 337(3), 164 - 70 Synthesis and biological testing of novel analogues of sydnone as potential antibacterial agents; Moustafa MA et al.; Several series of 3-phenylsydnone derivatives conjugated to well-known moieties with antibacterial activity were synthesized via several routes . These derivatives include 3-cyano-2-oxopyridine, 2-amino-3-cyanopyridine, 2-arylidene-1-ethylidenehydrazine and 2-aroyl-1-ethylidenehydrazine moieties . Thus, the key intermediate 3-(4-acetylphenyl)sydnone (3) was allowed to react with the appropriate aldehyde, ethyl cyanoacetate or malononitrile in presence of excess ammonium acetate in two steps (method 1) or through a one-pot reaction technique (methods 2 and 3) to give the corresponding sydnone derivatives 5 and 6, respectively . Moreover, condensation of compound 3 with hydrazine hydrate followed by the reaction with the appropriate aldehyde, mono- and dicarboxylic acid hydrazide yielded the corresponding sydnone derivatives 8, 9 and 10, respectively . Most of the synthesized compounds were screened for their in vitro antibacterial activity against various pathogenic organisms of both Gram-positive and Gram-negative bacteria . The minimum inhibitory concentrations (MICs) were determined using agar dilution method. Int J Antimicrob Agents, 2004 Mar, 23 Suppl 1, S83 - 7 Single-drug or combined antibacterial therapy in the treatment of patients with chronic prostatitis and Chlamydia trachomatis? Smelov V, Gorelov A, Smelova N, Krylova T. The efficacy of antibacterial combinations as compared with single-drug treatment in 57 patients with chronic prostatitis and Chlamydia trachomatis was investigated in this study. Int J Antimicrob Agents, 2004 Mar, 23 Suppl 1, S79 - 82 Azithromycin treatment follow-up: antibacterial susceptibility of Chlamydia trachomatis in patients with chronic prostatitis; Smelov V et al.; The antibacterial susceptibility of Chlamydia trachomatis in 138 patients with chronic prostatitis (CP) and clinical failures after antibacterial treatment with azithromycin (AZI) were investigated . Azithromycin was not found to be top-of-the-line drug in the follow-up treatment, showing only average results in vitro . The investigation of the susceptibility of chlamydia to antibiotics in causes of chronic prostatitis is highly recommended. Toxicon, 2004 Mar 1, 43(3), 311 - 8 Anti-Plasmodium properties of group IA, IB, IIA and III secreted phospholipases A2 are serum-dependent; Guillaume C et al.; Antibacterial, antiparasitidal and antiviral properties have recently been attributed to members of the secreted phospholipases A(2) (sPLA(2)s) superfamily . Seven sPLA(2)s from groups IA, IB, IIA and III, were tested here in different culture conditions for inhibition of the in vitro intraerythrocytic development of Plasmodium falciparum, the causative agent of the most severe form of human malaria . In the presence of human serum, all sPLA(2)s were inhibitory, with three out of seven exhibiting IC(50)<0.1 nM . In all cases, inhibition could be induced by enzymatic pre-treatment of the serum . By contrast, no effect was observed when parasites were grown in a semi-defined medium (AlbuMAX II) devoid of lipoproteins and containing 10 times less phospholipids than the medium with human serum, strongly suggesting that hydrolysis of serum generating toxic lipid by-products, rather than a direct interaction of the sPLA(2) with the infected erythrocyte, is a general feature of the anti-Plasmodium properties of sPLA(2)s . Furthermore, in serum, six out of the seven sPLA(2)s were toxic against both trophozoite and schizont stages of the parasite development, contrasting with the trophozoite-selective bee venom enzyme's toxicity . Deciphering the molecular mechanisms at play in the phenotypic singularity of the bee venom enzyme toxicity might offer new prospects in antimalarial fight. Pharm Res, 2004 Feb, 21(2), 330 - 8 Effect of cisplatin-induced acute renal failure on bioavailability and intestinal secretion of quinolone antibacterial drugs in rats; Yamaguchi H et al.; PURPOSE: The aim of this study was to clarify the effects of renal failure on intestinal secretion of quinolone antibacterial drugs . METHODS: Pharmacokinetics of grepafloxacin, levofloxacin, and ciprofloxacin in cisplatin-induced acute renal failure (ARF) rats were evaluated, and intestinal and biliary clearance studies were examined . Transport experiments using culture cells were performed . RESULTS: The bioavailability of grepafloxacin in ARF rats was 1.2-fold higher than that in normal rats . On the other hand, the bioavailability of ciprofloxacin in ARF rats was markedly decreased to half of that in normal rats, and that of levofloxacin was not changed . Intestinal clearance of grepafloxacin in ARF rats was 75% of that in normal rats, whereas that of ciprofloxacin was 1.4-fold higher than in normal rats, and that of levofloxacin was comparable between normal and ARF rats . Transport experiments using P-glycoprotein-expressing LLC-GA5-COL150 cells and human intestinal Caco-2 cells suggested that grepafloxacin and levofloxacin were substrates of P-glycoprotein and that ciprofloxacin was not, and that intestinal secretion of ciprofloxacin was mediated by a specific transport system distinct from organic cation and anion transporters and multidrug resistance-associated protein 2 . CONCLUSIONS: Cisplatin-induced ARF differentially modulated the bioavailability and intestinal secretion of quinolones in rats. Fitoterapia, 2004 Mar, 75(2), 228 - 30 Antibacterial compounds from the seeds of Psoralea corylifolia; Khatune NA et al.; Psoralidin, bakuchicin, psoralin and angelicin, isolated from the seeds of Psoralea corylifolia, showed significant antibacterial activities against a number of Gram (+) and Gram (-) bacteria. Fitoterapia, 2004 Mar, 75(2), 204 - 8 Antibacterial activities of some constituents from oleo-gum-resin of Commiphora mukul; Saeed MA et al.; The essential oil, chloroform extract and seven sesquiterpenoids compounds newly isolated from the oleo-gum-resin of Commiphora mukul showed a wide range of inhibiting activity against both Gram (+) and Gram (-) bacteria. J Agric Food Chem, 2004 Mar 24, 52(6), 1514 - 9 Relationship between antibacterial activity of (+)-catechin derivatives and their interaction with a model membrane; Kajiya K et al.; (+)-Catechin derivatives with different alkyl chain lengths were synthesized from (+)-catechin and various straight chain alkylaldehydes in the presence of methyl mercaptan, and their antibacterial activities against Gram-positive bacteria were evaluated . The antibacterial activity increased markedly with elongation of the alkyl chain lengths of the derivatives and reached a maximum at a chain of four to seven carbons . Subsequently, interaction of the (+)-catechin derivatives with a model membrane using liposome was investigated . The derivatives with a chain of three carbons or more were found to have very strong affinity for the membrane . The injury action of the derivatives against the membrane was examined with liposome in which calcein was enclosed as a fluorescent indicator . The leakage was observed in the derivatives with chain lengths of four carbons or more . Particularly the derivatives with chains longer than five carbons are considered to destroy the liposome membrane judging from the degree of the fluorescent leakage . These results implied that the lipophilicity and disrupting ability of the (+)-catechin derivatives to the liposome membrane participate in their antibacterial activity. Vestn Otorinolaringol, 2004, (1), 49 - 50 {Comparative efficacy and safety of amoxiclav (amoxicillin clavulanate) and ampicillin in the treatment of acute bacterial sinusitis}; Kriukov AI et al.; Efficacy and safety of amoxiclav (amoxicillin clavulanate) and ampicillin were studied in antibacterial therapy of acute sinusitis . Antibacterial efficacy of amoxiclav in acute sinusitis reached 100% . Its safety was good . Antibacterial efficacy of ampicillin was 76%; 24% patients retained symptoms of the disease, x-ray picture of sinusitis . Its toxicity was higher. Vestn Otorinolaringol, 2004, (1), 39 - 41 {Pre- and intraoperative preparation of patients with pyoinflammatory diseases of the ear, pharynx and paranasal sinuses}; Kriukov AI et al.; The authors consider the problems of effective general and local antibiotic therapy regarding most frequently occurring now causative agents and doses of antibacterial drugs . Combined use of antibacterial drugs and immunostimulators is analysed as antibacterial drugs deteriorate nonspecific immunity. Vestn Otorinolaringol, 2004, (1), 35 - 8 {Current antibacterial therapy of acute otitis media}; Turovskii AB et al.; General approaches to general and local therapy of acute otitis media are validated and schemes of antibacterial treatment of this disease are proposed. Vestn Otorinolaringol, 2004, (1), 33 - 4 {Bacterial contamination of the maxilla after radical surgical treatment}; Pal'chun VT et al.; Qualitative and quantitative examinations of the microflora in a postoperative cavity of 62 patients early after radical surgery on the maxilla with opening of the ethmoidal labyrinth have found that in spite of a noticeable antibacterial effect of the operation pyoinflammatory process in the wound is possible . Treatment basing on bacteriological findings is recommended. Vestn Otorinolaringol, 2004, (1), 28 - 32 {The role of chlamydial infection in development of acute respiratory diseases in children}; Savenkova MS et al.; The examination of 245 children with respiratory diseases has detected chlamydia in 45 (18.4%) of them . Chlamydial species were identified and clinical symptoms of acute respiratory diseases (ARD) of chlamydial etiology are described . Five serological groups of patients depending on the presence or absence of chlamydial infection markers were recognized . Antibacterial drug treatment showed that most effective were sumamed, rulid and clindamycin . Long-term outcomes in relation to the kind of treatment are analysed. Vestn Otorinolaringol, 2004, (1), 5 - 14 {Effective antibacterial therapy in otorhinolaryngology: bacteriological rationale}; Zhukhovitskii VG; The article presents current views on etiopathogenesis of the diseases associated with contamination with microorganisms; reviews inflammatory ENT diseases in terms of current literature on clinical microbiology of these diseases; characterizes microorganisms more or less specific for each relevant nosological entity; analyses basic groups of antibacterial drugs with formulation of bacteriologically grounded principles of initial antibacterial therapy of ENT inflammation. Bioorg Med Chem Lett, 2004 Apr 5, 14(7), 1811 - 5 Preliminary in vitro studies on two potent, water-soluble trimethoprim analogues with exceptional species selectivity against dihydrofolate reductase from Pneumocystis carinii and Mycobacterium avium; Forsch RA et al.; 2,4-Diamino-5-{3',4'-dimethoxy-5'-(5-carboxy-1-pentynyl)}benzylpyrimidine (6) and 2,4-diamino-5-{3',4'-dimethoxy-5'-(4-carboxyphenylethynyl)benzylpyrimidine (7) were synthesized from 2,4-diamino-5-(5'-iodo-3',4'-dimethoxybenzyl)pyrimidine (9) via a Sonogashira reaction with appropriate acetylenic esters followed by saponification, and were tested as inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinii (Pc), Toxoplasma gondii (Tg), Mycobacterium avium (Ma), and rat in comparison with the widely used antibacterial agent 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine (trimethoprim, TMP) . The selectivity index (SI) for each compound was calculated by dividing its 50% inhibitory concentration (IC(50)) against rat DHFR by its IC(50) against Pc, Tg, or Ma DHFR . The IC(50) of 6 against Pc DHFR was 1.0 nM, with an SI of 5000 . Compound 7 had an IC(50) of 8.2 nM against Ma DHFR, with an SI of 11000 . By comparison, the IC(50) of TMP was 12000 nM against Pc, 300 nM against Ma, and 180000 against rat DHFR . The potency and selectivity values of 6 and 7 were not as high against Tg as they were against Pc or Ma DHFR, but nonetheless exceeded those of TMP . Because of the outstanding selectivity of 6 against Pc and of 7 against Ma DHFR, these novel analogues may be viewed as promising leads for further structure-activity optimization. Bioconjug Chem, 2004 Mar-Apr, 15(2), 333 - 43 Immobilization of a novel antibacterial agent on solid phase and subsequent isolation of EF-Tu; Deibel MR Jr et al.; Screening of our compound collection identified PNU-92560, a 2-{1,3,4}thiadiazolo{3,2-a}pyrimidine-6-carboxamide, as a novel antibacterial agent . Extensive analogue development identified that the 2-position of the thiadiazole could be functionalized with a linker that would allow the compound to be attached to a solid support . The extreme insolubility of the analogues prevented the mechanism of action for these compounds to be determined utilizing traditional methodology . The solid-supported compounds were utilized as affinity columns to identify elongation factor Tu (EF-Tu) as a putative target for this class of compounds . The activity of the compounds in a metabolic labeling experiments and in translation assay supports the identity of the target for these compounds to be EF-Tu. Biomaterials, 2004 Aug, 25(17), 3689 - 98 Evaluation of antibiotic-loaded collagen-hyaluronic acid matrix as a skin substitute; Park SN et al.; The 1-ethyl-(3-3-dimethylaminopropyl) carbodiimide hydrochloride-crosslinked collagen-hyaluronic acid (HA) matrices containing tobramycin or ciprofloxacin as an antibiotic agent were fabricated for the control of wound contamination and characterized with respect to morphology, mechanical strength, in vitro release, antibacterial activity and cytotoxicity . For the tobramycin loaded matrix, the antibacterial capacity increased with the drug loading . Tobramycin and ciprofloxacin loaded matrices maintained their antibacterial effects for over 96 and 48 h, respectively . However, cell viability testing revealed that 0.4 mg/ml of ciprofloxacin has a cytotoxic effect on fetal human dermal fibroblasts . The effects of the bilayered collagen-HA matrices containing tobramycin and growth factors were also evaluated using an in vivo full thickness dermal defect model . Though the tobramycin incorporated collagen-HA matrix had no significant effect on wound healing compared with the control, the tobramycin incorporated matrix containing basic fibroblast growth factor or platelet-derived growth factor significantly enhanced wound healing . This study demonstrates the potential efficacy of crosslinked collagen-HA matrix containing antibiotics and growth factors for defective skin tissue replacement and infection prevention. Peptides, 2003 Nov, 24(11), 1779 - 84 The antibacterial peptide ceratotoxin A displays alamethicin-like behavior in lipid bilayers; Saint N et al.; Ceratotoxin A (CtxA), a 36-residue alpha-helical cationic peptide isolated from the medfly Ceratitis capitata, exhibits strong antibacterial activity . To determine its mode of action against bacteria, we investigated the behavior of ceratotoxin A by incorporating it into planar lipid bilayers . Macroscopic and single channel conductance experiments showed that ceratotoxin A forms voltage-dependent ion channels in bilayers according to the barrel-stave model . The characteristics of the channel suggest that the C-terminal regions form bundles of five or six helices embedded in the membrane, such that the N-terminal moieties lie on the polar side of the lipid bilayer. Peptides, 2003 Nov, 24(11), 1753 - 61 Membrane binding and permeation by indolicidin analogs studied by a biomimetic lipid/polydiacetylene vesicle assay; Halevy R et al.; Membrane binding and relative penetration of indolicidin analogs were studied using lipid/polydiacetylene (PDA) chromatic biomimetic membranes . Colorimetric and fluorescence analyses determined that an indolicidin analog with a proline and tryptophan residue substituted with lysines showed more pronounced bilayer surface interactions, while indolicidin and particularly an indolicidin analog in which all prolines were replaced with alanine residues exhibited deeper insertion into the lipid bilayer . The colorimetric data demonstrated that more pronounced blue-red transitions were observed when the chromatic vesicles incorporated lipopolysaccharide (LPS) within the lipid bilayer, indicating that LPS promoted preferred binding and incorporation of the peptides at the lipid/water interface . The fluorescence quenching experiments further confirmed this outcome . The results indicate that the antibacterial activity of indolicidin most likely requires initial binding to the LPS moieties within bacterial membranes, as well as disruption of the bilayer interface . The degree of hemolysis induced by the analogs, on the other hand, correlated to the extent of penetration into the hydrophobic core of the lipid assembly. Peptides, 2003 Nov, 24(11), 1713 - 21 A peptidylprolyl cis/trans isomerase from Xenopus laevis skin: cloning, biochemical characterization and putative role in the secretion; Miele R et al.; In amphibian skin secretions, a peptidylprolyl cis/trans isomerase activity was detected . A Xenopus laevis skin cDNA coding for this protein was cloned, sequenced and over-expressed in Escherichia coli . The primary structure of the protein shows extensive similarity with members of the cyclophilin A family . Catalytic parameters of the recombinant protein are similar to those of the human enzyme . The enzymatic activity is inhibited by cyclosporin A . Data suggesting that peptidylprolyl isomerization influences the biological activity of antibacterial peptides of amphibian origin are presented, and its putative role in the defence mechanism discussed. Bull Soc Pathol Exot, 2003 Jan, 96(5), 376 - 82 {Management of mycetoma in West-Africa}; Develoux M et al.; Mycetoma is still endemic in the northern areas of West-Africa . This infection is more common in males, rural inhabitants, between 20 and 40 years of age . Mycetoma is generally easy to identify on clinical presentation, it is a chronic subcutaneous inflammatory tumor with discharging sinuses . The commonest affected site is the foot (70%), leg, knee, thigh, hand and arm are the most frequent extrapodal localizations . Diagnosis must be confirmed by the presence of grains at direct and histological examinations . It is indispensable to distinguish actinomycetoma (caused by aerobic bacteria) and eumycetoma (caused by fungi) as their treatments are different . The main etiological agents in West-Africa: Streptomyces somaliensis, Actinomadura pelletieri, Actinomadura madurae (actinomycetes), Madurella mycetomatis and Leptosphaeria sp (fungi) can be identified in most cases by histological examination of the grain . In the West Sahelian belt actinomycetoma is more frequent than eumycetoma except in Mauritania . When a mycetoma is diagnosed it is fundamental to determine as precisely as possible the extent of the lesion . Bone involvement is the major complication and must be systematically investigated by radiology . Mycetoma has characteristic ultrasonographic features, ultrasonographic technique appears to be very useful in medical centers where no mycological tests can be done . Ultrasonography is also an accurate technique to delimit the extent of the process . Computed tomography is also sensitive to assess the extent of mycetoma in soft tissues and can detect early bone involvement but is more onerous than ultrasonography . Ketoconazole or itraconazole in combination with surgery is recommended for eumycetoma patients . Actinomycetoma responds to antibacterial agents, different therapeutic schemes can be proposed and depend on the etiological agent. J Antibiot (Tokyo), 2003 Dec, 56(12), 1033 - 44 Novel alpha-pyrones produced by a marine Pseudomonas sp . F92S91: taxonomy and biological activities; Singh MP et al.; Inhibitors of the enzymes involved in fatty acid biosynthesis (FAB) have been reported as antibacterial agents . These include thiolactomycin, cerulenin, triclosan, diazoborine, naphthyridinones, aminopyridines and pyridoindoles . Our search for new FAB inhibitors, using a lacZ reporter cell-based screen, led to several confirmed hits . Culture F92S91, later identified as a Pseudomonas sp . based on 16S profiling, was found to produce two alpha-pyrones (I and II) and three high molecular weight peptides . The pyrones were unstable under acidic conditions, and they were rearranged into a furanone derivative (III) . Of these compounds, pyrone I was the most active with MICs (microg/ml) against B . subtilis (1 to approximately 2), MRSA (2 to approximately 4), M . catarrhalis (4) and VRE (2 to approximately 64) . Effects on macromolecular synthesis and membrane functions were tested in B . subtilis . Pyrone I nonspecifically inhibited incorporation of radiolabeled precursors into DNA, RNA and protein within 5 minutes of drug exposure, similar to that of triclosan . Both compounds also inhibited the cellular uptake of these precursors . Cerulenin did not have an effect until 30 minutes of drug treatment . Pyrone I and triclosan were membrane-active (BacLight test); however, pyrone I (at < or = 128 microg/ml concentration) was not hemolytic to human RBCs in contrast to triclosan, which was hemolytic at 16 microg/ml . These data suggest that pyrone-I, unlike triclosan, selectively affects bacterial membrane function. Fundam Clin Pharmacol, 2003 Dec, 17(6), 691 - 701 Clarithromycin reduces Isus and Ito currents in human atrial myocytes with minor repercussions on action potential duration; Gluais P et al.; The macrolide antibacterial agent clarithromycin has been shown to cause QT interval prolongation on the electrocardiogram . In rabbit heart preparations clarithromycin (concentration dependently) lengthened the action potential duration and blocked the delayed rectifier current . The aim of the present study was to investigate the clarithromycin effects: (i) on the Ca2+ L-type and the main K+ repolarizing currents on human atrial myocytes, using whole-cell patch clamp recordings and (ii) on action potentials recorded from human atrial and ventricular myocardium using conventional microelectrodes . It has been found that (i) 10-30 microM clarithromycin reduced the sustained current Isus significantly and that a 100 microM concentration was needed to cause a significant reduction in the transient outward current Ito, whereas clarithomycin did not affect the calcium current and (ii) clarithromycin (10-100 microM) prolonged the action potential duration in atrial preparations but did not alter the different parameters of the ventricular action potential . It is concluded that clarithromycin exerts direct cardiac electrophysiological effects that may contribute to pro-arrythmic potential. Zhongguo Zhong Yao Za Zhi, 2003 Mar, 28(3), 196 - 8 {Advance of chemical constituents and bioactivity of Saururuaceae plants}; Ma L et al.; Essential oil, flavonoids, alkaloids and lignas were isolated from Saururuaceae plants . They possesses antibacteral, antiviruses, antiinflammatory . Inhibitory of plaleted aggregation activites and exhibit significant neuroleptic activity. Am J Ophthalmol, 2004 Mar, 137(3), 554 - 6 Ocular vaccinia following exposure to a smallpox vaccinee; Hu G et al.; PURPOSE: To describe the presentation and management of the first identified case of ocular vaccinia infection associated with the current smallpox vaccination program . DESIGN: Case report . METHODS: Vaccinia virus was isolated by cell culture of a conjunctival swab . Direct staining with fluorescein isothiocyanate-labeled vaccinia antibody and polymerase chain reaction testing confirmed the diagnosis . RESULTS: In February 2003, a 26-year-old woman developed right preseptal cellulitis and blepharoconjunctivitis following contact with a vaccinated member of the military . The preseptal cellulitis resolved with antibacterial therapy, and the conjunctival infection was treated successfully with a 14-day course of topical trifluridine and a single dose of intravenous vaccinia immune globulin . CONCLUSIONS: To facilitate rapid diagnosis and appropriate treatment, clinicians must maintain a high index of suspicion for ocular smallpox vaccine-associated adverse reactions in vaccine recipients and their close contacts. FEBS Lett, 2004 Mar 12, 561(1-3), 181 - 5 The existence of a putative post-transcriptional regulatory element in 3'-UTR of Drosophila antibacterial peptide diptericin's mRNA; Chen HX et al.; Antibacterial peptides' genes are rapidly and transiently expressed on immune stimulation, which is the characteristic of immediate early genes . It implies post-transcriptional regulation is an important pathway in antibacterial peptides' gene expression . In a search of putative post-transcriptional regulatory elements, we found a segment of an AU-rich sequence in 3'-untranslated region (UTR) of drosophila diptericin mRNA . 3'-UTR of diptericin mRNA can be specifically bound with Elav and this binding can be competed with the typical AU-rich element (ARE) of c-fos mRNA . These results suggest that the AU-rich sequence in the 3'-UTR of diptericin mRNA may be a cis-acting element and involved in post-transcriptional regulation. Drugs Aging, 2004, 21(4), 211 - 28 Epidemiology and management of diverticular disease of the colon; Kang JY et al.; Colonic diverticula are protrusions of the mucosa through the outer muscular layers, which are usually abnormally thickened, to form narrow necked pouches . Diverticular disease of the colon covers a wide clinical spectrum: from an incidental finding to symptomatic uncomplicated disease to diverticulitis . A quarter of patients with diverticulitis will develop potentially life-threatening complications including perforation, fistulae, obstruction or stricture . In Western countries diverticular disease predominantly affects the left colon, its prevalence increases with age and its causation has been linked to a low dietary fibre intake . Right-sided diverticular disease is more commonly seen in Asian populations and affects younger patients . Its pathogenesis and relationship to left-sided diverticular disease remains unclear . Diverticular disease of the colon is a significant cause of morbidity and mortality in the Western world and its frequency has increased throughout the whole of the 20th century . Since it is a disease of the elderly, and with an aging population, it can be expected to occupy an increasing portion of the surgical and gastroenterological workload . It is uncertain what symptoms uncomplicated diverticular disease gives rise to: there is an overlap with irritable bowel syndrome . Diagnosis is primarily by barium enema and colonoscopy, but more sophisticated imaging procedures such as computed tomography (CT) are increasingly being used to assess and treat complications such as abscess or fistula, or to provide alternative diagnoses if diverticulosis is not confirmed.Initial therapy for uncomplicated diverticulitis is supportive, including monitoring, bowel rest and antibacterials . CT is used to guide percutaneous drainage of abscesses to avoid surgery or allow it to be performed as an elective procedure . Surgery is indicated for complications of acute diverticulitis, including failure of medical treatment, gross perforation, and abscess formation that cannot be resolved by percutaneous drainage . Complications of chronic diverticulitis (fistula formation, stricture and obstruction) are also usually treated surgically . However, the indications for, and the timing and staging of operations for diverticular disease are often difficult decisions requiring sound clinical judgement . Factors such as the number of episodes of inflammation, the age of the patient, and his/her overall medical condition play a role in determining whether or not a patient should undergo surgical resection . Laparoscopic surgery may be associated with less pain, less morbidity and shorter hospital stays, but its exact role is yet to be defined . Diverticular disease of the colon is the most common cause of acute lower gastrointestinal haemorrhage, which can be massive . Although the majority of patients stop bleeding spontaneously, angiographic and surgical treatment may be required, while the place of endoscopic haemostasis remains to be established. Immunology, 2004 Mar, 111(3), 273 - 81 Human beta-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils; Niyonsaba F et al.; Neutrophils are the effector cells in both innate and adaptive immunity, where they perform the functions of phagocytosis and killing of bacteria . They respond to a large number of chemoattractants, but their response to epithelial cell-derived human beta-defensins (hBD) has not been investigated . Here we report that hBD-2, but not hBD-1, is a specific chemoattractant for tumour necrosis factor (TNF)-alpha-treated human neutrophils . The optimal concentration required for maximal chemotactic activity was 5 micro g/ml . The effect of hBD-2 on neutrophils was dependent on the G-protein-phospholipase C pathway, as demonstrated by inhibition by pertussis toxin and U-73122 . In addition, ligand-receptor analysis indicated that the binding of hBD-2 was markedly inhibited by macrophage inflammatory protein (MIP)-3alpha, a specific and unique ligand for CCR6 . Furthermore, anti-CCR6 antibody could almost completely suppress the cell migration induced by hBD-2, suggesting that hBD-2 mainly utilizes CCR6 as a functional receptor . Thus, our finding that hBD-2 is a potent chemoattractant for human neutrophils through specific receptors provides a novel mechanism by which this peptide contributes to the host defence system by recruiting neutrophils to inflammation/infection sites . This also suggests an important link between epithelial cell-derived antibacterial peptides and neutrophils during infection or inflammation. J Evol Biol, 2004 Mar, 17(2), 421 - 9 Costs of resistance: genetic correlations and potential trade-offs in an insect immune system; Cotter SC et al.; Theory predicts that natural selection will erode additive genetic variation in fitness-related traits . However, numerous studies have found considerable heritable variation in traits related to immune function, which should be closely linked to fitness . This could be due to trade-offs maintaining variation in these traits . We used the Egyptian cotton leafworm, Spodoptera littoralis, as a model system to examine the quantitative genetics of insect immune function . We estimated the heritabilities of several different measures of innate immunity and the genetic correlations between these immune traits and a number of life history traits . Our results provide the first evidence for a potential genetic trade-off within the insect immune system, with antibacterial activity (lysozyme-like) exhibiting a significant negative genetic correlation with haemocyte density, which itself is positively genetically correlated with both haemolymph phenoloxidase activity and cuticular melanization . We speculate on a potential trade-off between defence against parasites and predators, mediated by larval colour, and its role in maintaining genetic variation in traits under natural selection. Jpn J Antibiot, 2003 Dec, 56(6), 719 - 36 {Use of the antibacterial agent levofloxacin for acute upper respiratory tract infection accompanied by fever (> or = 38 degrees C)}; Yamaguchi H et al.; The appropriate administration method of levofloxacin in relation to symptoms was investigated by following up 2,353 patients prescribed either levofloxacin (300 mg divided into 3 doses) or 400 mg (divided into 2 doses) for the treatment of acute upper respiratory tract infection accompanied by fever (temperature (> or = 38 degrees C) of suspected bacterial infection . 1) The cure rate based on body temperature as an index was significantly higher in the group administered 400 mg/day compared with the group administered 300 mg/day . No significant difference between the two regimens was observed in patients with a temperature < or = 38.5 degrees C at the start of administration, but patients with a temperature > or = 38.6 degrees C showed a significantly higher cure rate when administered 400 mg/day compared with 300 mg/day . 2) No significant difference between the groups was observed with respect to the improvement of quality of life (QOL), assessed using a VAS . In patients with a temperature > or = 38.6 degrees C, however, significantly higher improvement rates were demonstrated on days 3, 5 and 6 of treatment at 400 mg/day compared with 300 mg/day . 3) The reconsultation rate was significantly lower in the group administered 400 mg/day compared with the group administered 300 mg/day . No significant difference between the groups was observed in patients with a temperature < or = 38.5 degrees C . However, in the patients with a temperature > or = 38.6 degrees C, treatment at 400 mg/day achieved a significantly lower reconsultation rate compared with 300 mg/day . 4) Nonsteroidal anti-inflammatory drugs (NSAIDs) were concomitantly administered to 64.3% of the patients, but no significant difference in the cure rate was observed between patients with or without concomitant use of NSAIDs . 5) Among all of the patients, 12.7% were positive for the influenza virus, and anti-influenza drugs were concomitantly administered to 41.3% of them . However, no significant difference in the cure rate was observed between the group administered levofloxacin alone and the group concomitantly administered anti-influenza drugs . 6) The incidence of adverse drug reactions was 0.84% in the group administered 400 mg/day and 0.50% in the group administered 300 mg/day . No significant difference was observed between these groups and no serious adverse drug reactions occurred . In conclusion, for treating patients with acute upper respiratory tract infection accompanied by fever (> or = 38.6 degrees C) and suspected bacterial infection, levofloxacin dosage of 400 mg/day (divided into 2 doses) was superior to 300 mg/day (divided into 3 doses) in terms of therapeutic effect, QOL, and the reconsultation rate . This was considered to be an administration method worth recommending, including its safety . In patients with a temperature of 38.0 degrees C to 38.5 degrees C, administration of levofloxacin at 300 mg/day was confirmed to demonstrate a sufficient therapeutic effect. Jpn J Antibiot, 2003 Dec, 56(6), 674 - 80 {Comparative antibacterial activity of carbapenems against P . aeruginosa (2)}; Hikida M et al.; Susceptibility testing of 288 clinical isolates of P . aeruginosa in 2000 was performed by the disk diffusion method with observation at regular time course . Detailed analysis of the shape of the zones of inhibition gave interesting results, i.e . double zone of inhibition was found in MEPM specifically, unlike BIPM and IPM . The incidence was 50% . Moreover same phenomenon was detected in CAZ . After analyzing this phenomenon from the results of short-time-killing curve and inducibility of AmpC beta-lactamase it seems that there is a close relationship between formation of double zone of inhibition and bactericidal activity in sub-MIC drug concentration. J Allergy Clin Immunol, 2004 Mar, 113(3), 519 - 27 Drug interaction with T-cell receptors: T-cell receptor density determines degree of cross-reactivity; Depta JP et al.; BACKGROUND: Immune-mediated adverse reactions to drugs are often due to T-cell reactivity, and cross-reactivity is an important problem in pharmacotherapy . OBJECTIVE: We investigated whether chemical inert drugs can stimulate T cells through their T-cell receptor (TCR) and analyzed the cross-reactivities to related compounds . METHODS: We transfected human TCRs isolated from two drug-reactive T-cell clones (TCCs) by PCR into a TCR-negative mouse T-cell hybridoma . The TCCs were isolated from a patient with drug hypersensitivity to the antibacterial sulfonamide sulfamethoxazole (SMX) . RESULTS: The transfectants reacted to SMX only in the presence of antigen-presenting cells (APCs) . Glutaraldehyde-fixed APCs, however, were sufficient to elicit T-cell stimulation, indicating a processing-independent direct interaction of the drug with the TCR and MHC molecule . The transfected hybridomas secreted IL-2 in a drug dose-dependent manner, whereas the degree of reactivity was dependent on the level of TCR expression . One transfectant reacted not only to SMX but also to related sulfonamide compounds . Interestingly, high TCR expression increased cross-reactivity to other structurally related compounds . In addition, SMX-specific TCR cross-reacted only with sulfonamides bearing a sulfanilamide core structure but not with sulfonamides such as celecoxib, furosemide, or glibenclamide . CONCLUSIONS: These results demonstrate that the T-cell reactivity to drugs is solely determined by the TCR . Moreover, these results show that cross-reactivity of structurally similar compounds correlates with the density of the TCR . Stably transfected T-cell hybridomas may represent a powerful screening tool for cross-reactivity of newly generated sulfonamide-containing compounds such as celecoxib. Bioorg Med Chem Lett, 2004 Mar 22, 14(6), 1427 - 31 Design and synthesis of indolo{2,3-a}quinolizin-7-one inhibitors of the ZipA-FtsZ interaction; Jennings LD et al.; The binding of FtsZ to ZipA is a potential target for antibacterial therapy . Based on a small molecule inhibitor of the ZipA-FtsZ interaction, a parallel synthesis of small molecules was initiated which targeted a key region of ZipA involved in FtsZ binding . The X-ray crystal structure of one of these molecules complexed with ZipA was solved . The structure revealed an unexpected binding mode, facilitated by desolvation of a loosely bound surface water. Bioorg Med Chem Lett, 2004 Mar 22, 14(6), 1423 - 6 The discovery of biaryl acids and amides exhibiting antibacterial activity against Gram-positive bacteria; Look GC et al.; Solid-phase synthetic methods for biaryl-based compounds were developed resulting in the construction of two 1000-member libraries . Numerous compounds were identified by high-throughput screening using whole cell screens to exhibit anti-microbial activity against Gram-positive bacteria . A series of biaryl compounds containing natural and unnatural amino acids were made to explore the SAR of the amino acid functionality. Clin Pharmacokinet, 2004, 43(4), 239 - 52 Clinical pharmacokinetics of quinupristin/dalfopristin; Bearden DT; Quinupristin/dalfopristin is a streptogramin antibacterial with a wide spectrum of Gram-positive antibacterial activity . The drug has minimal oral absorption and is administered intravenously as a fixed 30 : 70 ratio of quinupristin to dalfopristin . A linear relationship has been observed between the dose administered and maximum plasma concentrations . Single-dose administration of 7.5 mg/kg produced a maximal plasma concentration of 2.3-2.7 mg/L for quinupristin and 6.1-8.2 mg/L for dalfopristin . The area under the concentration-time curve (AUC) obtained with the same dose was 2.7-3.3 and 6.5-7.7 mg . h/L for quinupristin and dalfopristin, respectively . Repeated administration results in 13-21% increases in maximum plasma concentrations and 21-26% increases in AUC for both quinupristin and dalfopristin . Quinupristin and dalfopristin exhibit steady-state volumes of distribution of 0.46-0.54 and 0.24-0.30 L/kg, respectively . Quinupristin exhibits higher protein binding (55-78%) than dalfopristin (11-26%), though both entities distribute well into tissues . Concentrations exceeding those in blood have been reported for the kidney, liver, spleen, salivary glands and white blood cells of primates . Extravascular penetration, as measured in blister fluid, is 40-80% . Both quinupristin and dalfopristin are extensively metabolised via nonenzymatic reactions . Quinupristin is conjugated to form two active compounds, a cysteine moiety and a glutathione moiety . Dalfopristin is hydrolysed to the active metabolite pristinamycin IIA . The metabolites exert antibacterial activity similar to that of the parent compounds . Quinupristin/dalfopristin is excreted primarily in the faeces (75-77%), with lesser renal excretion (15-19%) . The elimination half-lives of quinupristin and dalfopristin are similar, and are 0.7-1.3 hours after single doses . The metabolites have slightly longer half-lives, ranging from 1.2 to 1.8 hours . With repeated doses, plasma clearance of quinupristin and dalfopristin is reduced by approximately 20% compared with single doses, resulting in clearances of 0.7-0.8 L/h/kg . Saturable protein binding has been hypothesised as a causative mechanism . Quinupristin/dalfopristin is an inhibitor of cytochrome P450 3A4, resulting in multiple drug interactions . Ciclosporin AUC increased by 5-222% when coadministered with quinupristin/dalfopristin . Careful monitoring of patients receiving drugs that are substrates of cytochrome P450 3A4 is suggested.Quinupristin/dalfopristin is administered at 7.5 mg/kg every 8-12 hours, depending upon the severity of infection . The pharmacodynamic parameter linked with antibacterial activity for quinupristin/dalfopristin appears to be the ratio of AUC to the minimal inhibitory concentration . The additional activity of a prolonged post-antibiotic effect may also be important for efficacy. J Immunol, 2004 Mar 15, 172(6), 3620 - 7 B cells are crucial for both development and maintenance of the splenic marginal zone; Nolte MA et al.; The splenic marginal zone is a unique compartment that separates the lymphoid white pulp from the surrounding red pulp . Due to the orchestration of specialized macrophages and B cells flanking a marginal sinus, this compartment plays an important role in uptake of blood-borne Ags and it gives the spleen its specialized function in antibacterial immunity . In this study, we demonstrate that both development and maintenance of this marginal zone is highly dependent on the presence of B cells . Spleens from B cell-deficient mice were found to lack both metallophilic and marginal zone macrophages as well as mucosal addressin cellular adhesion molecule-1+ sinus lining cells . Using an inducible Cre/loxP-driven mouse model in which mature B cells could be partially depleted by removal of the B cell receptor subunit Igalpha, we could show that the integrity and function of an established marginal zone was also dependent on the presence of B cells . This was confirmed in a transgenic model in which all B cells were gradually depleted due to overexpression of the TNF family member CD70 . The loss of all cellular subsets from the marginal zone in these CD70 transgenic mice was effectively prevented by crossing these mice on a CD27(-/-) or TCRalpha(-/-) background, because this prohibited the ongoing B cell depletion . Therefore, we conclude that B cells are not only important for the development, but also for maintenance, of the marginal zone . This direct correlation between circulating B cells and the function of the spleen implies an increased risk for B cell lymphopenic patients with bacterial infections. Aquat Toxicol, 2004 Apr 14, 67(2), 167 - 79 Effects of triclosan on the early life stages and reproduction of medaka Oryzias latipes and induction of hepatic vitellogenin; Ishibashi H et al.; Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is widely used as antibacterial agent in various industrial products, such as textile goods, soap, shampoo, liquid toothpaste and cosmetics, and often detected in wastewater effluent . In this study, the effects of TCS on the early life stages and reproduction of medaka (Oryzias latipes) were investigated . The 96-h median lethal concentration value of TCS for 24-h-old larvae was 602 microg/l . The hatchability and time to hatching in fertilized eggs exposed to 313 microg/l TCS for 14 days were significantly decreased and delayed, respectively . An assessment of the effects of a TCS 21-day exposure period on the reproduction of paired medaka showed no significant differences in the number of eggs produced and fertility among the control and 20, 100 and 200 microg/l TCS treatment groups . However, concentrations of hepatic vitellogenin were increased significantly in males treated with TCS at 20 and 100 microg/l . In the F(1) generations, although the hatching of embryos in the 20 microg/l treatment showed adverse effects, there was no dose-response relationship between hatchability and TCS treatment levels . These results suggest that TCS has high toxicity on the early life stages of medaka, and that the metabolite of TCS may be a weak estrogenic compound with the potential to induce vitellogenin in male medaka but with no adverse effect on reproductive success and offspring. J Comb Chem, 2004 Mar-Apr, 6(2), 230 - 8 Tetrahydrofuran-based amino acids as library scaffolds; Edwards AA et al.; A furanose sugar amino acid (SAA) has been utilized as a library scaffold for the first time . Two furanose SAA scaffolds were examined to illustrate their potential for derivatization . The resulting 99-member library contained three orthogonal points of diversification that allowed easy access to ethers and carbamates from a hydroxyl moiety, a range of ureas from an azide (via an amine), and a range of amides from a methyl ester . The novel amide formation (by displacement of the methoxide from the methyl ester moiety) was achieved in good yield and purity with high structural confidence . Full characterization of several library intermediates (including a crystal structure) was obtained . The library was submitted for antibacterial screening. J Dent, 2004 Mar, 32(3), 247 - 54 The effect of light-curing modes on the microleakage of cervical resin composite restorations; Kubo S et al.; OBJECTIVE: This study investigated the effect of light-curing modes on the microleakage of cervical resin composite restorations . METHODS: Eighty wedge-shaped cervical cavities, C-factor approximately 1.3, were prepared on the labial surface of bovine incisors . The cavities were treated with a two-step experimental self-etching primer adhesive system containing an antibacterial monomer (ABF), according to the manufacturer's instructions, and filled with a single increment of a hybrid resin composite . The restorations were allocated randomly into four groups of 20: Group 1-the restorations were light-cured for 40 s with a conventional light-curing unit (New Light VL-II); Group 2-the restorations were cured with Candelux using a two-step mode; Group 3-the restorations were cured with Astralis 7 using a ramping mode; Group 4-the restorations were light-cured for 3 s with a plasma arc light-curing unit (Wave Light) . Half of the specimens from each group were subjected to thermocycling (5-60 degrees C, 15 s dwell time, 5000 cycles) prior to immersion in 0.5% basic fuchsin . The teeth were sectioned and the degrees of dye penetration were scored . The data were analyzed with either the Kruskal-Wallis test or the Mann-Whitney U-test (p < 0.05) RESULTS: No significant differences were found in the microleakage scores among the light-curing modes used . The restorations tended to display more microleakage when they were subjected to thermocycling, but the differences were not statistically significant . CONCLUSIONS: These findings suggest that light-curing modes may have no effect on the microleakage of cervical cavities with a small C-factor, as is the case in this study. Clin Infect Dis, 2004 Mar 15, 38(6), 864 - 70 Epub 2004 Mar 01. Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections; Pankey GA et al.; The distinction between bactericidal and bacteriostatic agents appears to be clear according to the in vitro definition, but this only applies under strict laboratory conditions and is inconsistent for a particular agent against all bacteria . The distinction is more arbitrary when agents are categorized in clinical situations . The supposed superiority of bactericidal agents over bacteriostatic agents is of little relevance when treating the vast majority of infections with gram-positive bacteria, particularly in patients with uncomplicated infections and noncompromised immune systems . Bacteriostatic agents (e.g., chloramphenicol, clindamycin, and linezolid) have been effectively used for treatment of endocarditis, meningitis, and osteomyelitis--indications that are often considered to require bactericidal activity . Although bacteriostatic/bactericidal data may provide valuable information on the potential action of antibacterial agents in vitro, it is necessary to combine this information with pharmacokinetic and pharmacodynamic data to provide more meaningful prediction of efficacy in vivo . The ultimate guide to treatment of any infection must be clinical outcome. Prostate Cancer Prostatic Dis, 2004, 7(1), 21 - 31 The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth; Ronquist G et al.; Prostasomes are submicron secretory granules synthesized, stored and secreted by the epithelial cells of the human prostate gland . They are membrane-surrounded also in their extracellular appearance and the membrane architecture is composite . They are believed to be life-giving and act as protectors of the spermatozoa in the lower and upper female genital tract on their way to the ovum . Hence, the prostasomes are immunosuppressive and inhibitory of complement activation . Further, they promote sperm's forward motility and have antioxidant and antibacterial capacities . The prostasomes with their many composite abilities seem to turn against the host cell after the age of 50 y being conducive to the transition of the normal prostate epithelial cell into a neoplastic cell and therewith lay the foundations of the very high prevalence of prostate cancer of men of more than 50 y of age. J Biochem (Tokyo), 2004 Jan, 135(1), 65 - 70 Antibacterial activity of peptides derived from the C-terminal region of a hemolytic lectin, CEL-III, from the marine invertebrate Cucumaria echinata; Hatakeyama T et al.; Several synthetic peptides derived from the C-terminal domain sequence of a hemolytic lectin, CEL-III, were examined as to their action on bacteria and artificial lipid membranes . Peptide P332 (KGVIFAKASVSVKVTASLSK-NH(2)), corresponding to the sequence from residue 332, exhibited strong antibacterial activity toward Gram-positive bacteria . Replacement of each Lys in P332 by Ala markedly decreased the activity . However, when all Lys were replaced by Arg, the antibacterial activity increased, indicating the importance of positively charged residues at these positions . Replacement of Val by Leu also led to higher antibacterial activity, especially toward Gram-negative bacteria . The antibacterial activity of these peptides was correlated with their membrane-permeabilizing activity toward the bacterial inner membrane and artificial lipid vesicles, indicating that the antibacterial action is due to perturbation of bacterial cell membranes, leading to enhancement of their permeability . These results also suggest that the hydrophobic region of CEL-III, from which P332 and its analogs were derived, may play some role in the interaction with target cell membranes to trigger hemolysis. Environ Sci Technol, 2004 Feb 15, 38(4), 1148 - 53 Pollution-induced community tolerance of soil microbial communities caused by the antibiotic sulfachloropyridazine; Schmitt H et al.; Little is known about the environmental hazards linked to the treatment of farm animals with antibiotics and subsequent spreading of manure, especially regarding soil microbial communities . In this investigation, pollution-induced community tolerance (PICT) of bacteria from soils artificially spiked with the sulfonamide sulfachloropyridazine (SCP) was investigated . Tolerance of the bacterial communities after 3 weeks' exposure to SCP was determined by analyzing the sensitivity of 31 microbial metabolic processes in microtiter plates . Bacterial suspensions extracted from soils containing higher concentrations of SCP showed an increased tolerance of their metabolic activities to this antibiotic . An increase in tolerance by 10% was found at 7.3 mg/kg dw SCP . The PICT effect could be demonstrated by both a shift in the tolerance of the average of all metabolic activities and a shift of the physiological process sensitivity distributions made up from the single metabolic processes . The PICT effect was accompanied by smaller changes in the community-level physiological profile (CLPP) . To conclude, PICT has been shown to be a versatile and illustrative method for the detection of the effects of antibacterial agents on soil microorganisms. Ann Intern Med, 2004 Mar 2, 140(5), 321 - 9 Effect of antibacterial home cleaning and handwashing products on infectious disease symptoms: a randomized, double-blind trial; Larson EL et al.; BACKGROUND: Despite the widespread household use of cleaning and personal hygiene products containing antibacterial ingredients, their effects on the incidence of infectious disease symptoms have not been studied . OBJECTIVE: To evaluate the effect of antibacterial cleaning and handwashing products for consumers on the occurrence of infectious disease symptoms in households . DESIGN: Randomized, double-blind clinical trial . SETTING: Northern Manhattan inner-city neighborhood, New York . PARTICIPANTS: 238 primarily Hispanic households (1178 persons) that included at least one preschool-age child . Interventions: Households were randomly assigned to use either antibacterial or nonantibacterial products for general cleaning, laundry, and handwashing . All products were commercially available, but the packaging was blinded and the products were provided free to participants . MEASUREMENTS: Hygiene practices and infectious disease symptoms were monitored by weekly telephone calls, monthly home visits, and quarterly interviews for 48 weeks . RESULTS: Symptoms were primarily respiratory: During 26.2% (717 of 2736) of household-months, 23.3% (640 of 2737) of household-months, and 10.2% (278 of 2737) of household-months, one or more members of the household had a runny nose, cough, or sore throat, respectively . Fever was present during 11% (301 of 2737) of household-months, vomiting was present in 2.2% (61 of 2737), diarrhea was present in 2.5% (69 of 2737), and boils or conjunctivitis were present in 0.77% (21 of 2737) . Differences between intervention and control groups were not significant for any symptoms (all unadjusted and adjusted relative risks included 1.0) or for numbers of symptoms (overall incidence density ratio, 0.96 {95% CI, 0.82 to 1.12}) . CONCLUSIONS: The tested antibacterial products did not reduce the risk for symptoms of viral infectious diseases in households that included essentially healthy persons . This does not preclude the potential contribution of these products to reducing symptoms of bacterial diseases in the home. Clin Ther, 2004 Jan, 26(1), 48 - 62 Efficacy and tolerability of once-daily oral telithromycin compared with clarithromycin for the treatment of community-acquired pneumonia in adults; Mathers Dunbar L et al.; BACKGROUND: Telithromycin is a new antibacterial agent of the ketolide class designed to provide optimal treatment against common bacterial respiratory tract pathogens . Telithromycin was derived by structural modification of the basic macrolide molecule to allow tight binding to the bacterial ribosome that enhances potency and minimizes the risk for the development of resistant strains . OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of telithromycin 800 mg once daily with those of high-dose clarithromycin (500 mg twice daily), each for 10 days, in the treatment of adult patients with community-acquired pneumonia (CAP) . METHODS: This randomized, double-blind, double-dummy, parallel-group clinical trial was conducted at 54 centers in the United States, Canada, Argentina, and Chile . Patients aged >or=18 years with acute CAP were randomized to receive 10-day treatment with oral telithromycin 800 mg once daily (administered as two 400-mg encapsulated tablets in the morning) and placebo (administered as 2 encapsulated tablets identical to the telithromycin in the evening) or high-dose clarithromycin (500 mg administered as two 250-mg identical encapsulated tablets twice daily) . The primary outcome measure was clinical outcome at the posttherapy, test-of-cure visit (days 17-24 after the completion of therapy) in the clinically assessable per-protocol population . Secondary efficacy variables included bacteriologic outcome at the posttherapy, test-of-cure visit, and clinical and bacteriologic outcomes at the late posttherapy visit (day 31-45) . Tolerability was assessed using investigator observation, patient self-reporting, clinical laboratory data, a 12-lead electrocardiogram, and physical examination (including vital signs) . RESULTS: A total of 493 patients were enrolled and 448 patients received >or=1 dose of study medication (224 patients/group) . A diagnosis of CAP was confirmed in 416 patients (205 men, 211 women; median age, 43 years; telithromycin, n = 204; clarithromycin, n = 212) . Clinical cure rates were 88.3% (143/162) in the telithromycin group and 88.5% ( 138/56) in the clarithromycin group . Bacterial eradication rates were comparable between treatment groups (telithromycin, (28/32) {87.5%}; clarithromycin, (29/30) {96.7%} . Both treatment were fairly well tolerated; adverse events were experienced in 57.0% of the patients treated with telithromycin and 49.1% of those treated with clarithromycin; most of these were assessed as mild . CONCLUSIONS: In this study of adult patients with CAP, telithromycin 800 mg once daily was an effective and fairly well-tolerated regimen for initial empiric treatment, with clinical and bacteriologic efficacy and tolerability equivalent to therapy with high-dose clarithromycin (500 mg twice daily). Ann Pharmacother, 2004 Apr, 38(4), 634 - 40 Epub 2004 Feb 27. Nitazoxanide treatment for giardiasis and cryptosporidiosis in children; Bailey JM et al.; OBJECTIVE: To review the pharmacology, pharmacokinetics, adverse effects, drug interactions, dosing recommendations, and clinical efficacy of nitazoxanide, a new antiprotozoal/anthelmintic/antibacterial agent . DATA SOURCES: A MEDLINE search (1966-February 2004) of both human and animal research data published in the English language was conducted . STUDY SELECTION AND DATA EXTRACTION: All primary and review articles pertaining to the MEDLINE search were reviewed for inclusion . Emphasis was placed on randomized, double-blind, placebo-controlled trials . DATA SYNTHESIS: Nitazoxanide is approved for the treatment of giardiasis and cryptosporidiosis (first drug approved for the latter indication) in immune-competent children <12 years of age . Most studies in immune-competent patients have reported clinical and parasitologic response rates close to 80% and 70%, respectively, for both indications . Response rates have been lower in immune-compromised patients . CONCLUSIONS: Nitazoxanide should be available for patients unable to tolerate or adhere to first-line therapy employed for these intestinal protozoa. Respirology, 2004 Mar, 9(S1), S56 - S59 Appendix II: How to use antibacterial agents in the elderly; Assessment of the efficacy of antibacterial agents; Assessment of the efficacy of antibacterial agents The committee for The Japanese Respiratory Society guidelines in management of respiratory infections . Respirology 2004; 9: S40-S42 Respirology, 2004 Mar, 9(S1), S16 - S24 Antibacterial therapy of hospital-acquired pneumonia; Novel antibacterial agents for skin and skin structure infections; Department of Dermatology, St . Luke's-Roosevelt Hospital Center, 1090 Amsterdam Avenue, New York, NY 10025, USAWith the continuing development of clinical drug resistance among bacteria and the advent of resistance to the recently released agents quinupristin-dalfopristin and linezolid, the need for new, effective agents to treat multidrug-resistant gram-positive infections remains important . With treatment options limited, it has become critical to identify antibiotics with novel mechanisms of activity . Several new drugs have emerged as possible therapeutic alternatives . This review focuses on agents newly introduced and those presently in clinical development for the treatment of skin and skin structure infections . Linezolid, quinupristin-dalfopristin, and daptomycin have been approved by the Food and Drug Administration for the treatment of skin and skin structure infections . Two newer compounds, oritavancin and dalbavancin, are in clinical development for this indication . In addition, the quinolones moxifloxacin and gatifloxacin recently were approved for cutaneous infections . Learning objective: At the conclusion of this learning activity, participants should be familiar with the modes of action, clinical indications, dosage regimens, and contraindications and cautions for several novel antibacterial agents for skin and skin structure infections. Transpl Infect Dis, 2003 Dec, 5(4), 167 - 73 Infectious complications in patients randomized to receive allogeneic bone marrow or peripheral blood transplantation; Nucci M et al.; Very few data are available on the comparison of infectious complications in peripheral blood stem cell transplantation (PBSCT) and bone marrow transplant (BMT) . The objective of this study was to evaluate the severity and frequency of infectious complications in patients randomized to receive PBSCT or BMT . We retrospectively reviewed the charts of all patients included in a randomized clinical trial comparing PBSCT (27 patients) and BMT (29 patients) . We analyzed two periods: pre-engraftment and post-engraftment . In the pre-engraftment period, we compared the two groups with respect to the duration of neutropenia, antibiotic use and hospitalization, and documentation of infection . In the post-engraftment period, we analyzed the occurrence and severity of graft-versus-host disease (GVHD), duration of cyclosporine, corticosteroids, antibiotic, antiviral and antifungal prophylaxis, number of episodes of infection, and death rates . Patients receiving PBSCT had shorter duration of neutropenia, but there were no differences in the incidence of infections or duration of antibiotic therapy . Patients receiving PBSCT had a higher incidence of extensive chronic GVHD (65% vs . 39%, P=0.08), longer duration of cyclosporine use (risk ratio {RR} 1.97), corticosteroids (RR 1.66), antibacterial (RR 2.60), antifungal (RR 2.50), anti-Pneumocystis carinii (RR 2.06) and anti-cytomegalovirus (RR 1.44) prophylaxis, and more infectious episodes (3.65 vs . 2.32 per 1000 days at risk, RR 1.57) . There were no differences in death rates . Multivariate analysis identified the use of steroids as the most significant variable associated with infectious episodes . PBSCT was associated with more infections in the post-engraftment period. J Fish Dis, 2004 Jan, 27(1), 57 - 64 A synthetic antibacterial peptide from Mytilus galloprovincialis reduces mortality due to white spot syndrome virus in palaemonid shrimp; Dupuy JW et al.; White spot syndrome virus (WSSV) isolated from Penaeus monodon was found to be highly infective for the western Mediterranean shrimp, Palaemon sp . Using polymerase chain reaction (PCR), it was demonstrated that such shrimp are not naturally carriers of WSSV . Following challenge with virus, mortality reached 100% 3.5-4 days after injection at 22 degrees C . Incubation of infected shrimp at 10 degrees C totally suppressed the mortality which rapidly developed when shrimp were returned to 18 or 22 degrees C . Preincubation of WSSV with mature synthetic mytilin significantly reduced shrimp mortality with a 50% efficient dose of about 5 microM . Survival of shrimp was not due to the development of an active mechanism of defence as re-injection of WSSV produced the same mortality pattern . Mortality was probably due to WSSV replication as dot blot failed to detect viral DNA in the injection sample but was positive 1 day post-injection . Protection by mytilin was by interaction at the virus level, preventing replication as no WSSV nucleic acid was detected by PCR even after 7 days in shrimp injected with WSSV preincubated with 10 or 50 microM mytilin. Antimicrob Agents Chemother, 2004 Mar, 48(3), 946 - 53 Activities of ciprofloxacin and moxifloxacin against Stenotrophomonas maltophilia and emergence of resistant mutants in an in vitro pharmacokinetic-pharmacodynamic model; Ba BB et al.; A two-compartment in vitro pharmacokinetic-pharmacodynamic model, with full computer-controlled devices, was used to accurately simulate human plasma pharmacokinetic profiles after multidose oral regimens of ciprofloxacin (750 mg every 12 h) and moxifloxacin (400 mg every 24 h) during 48 h . Pharmacodynamics of these drugs was investigated against three quinolone-susceptible strains of Stenotrophomonas maltophilia (MICs of ciprofloxacin and moxifloxacin of 0.5 to 2 and 0.0625 to 0.5 microg/ml, respectively) . The first dose of ciprofloxacin and moxifloxacin reduced the bacterial count by 1 and 2 log CFU/ml, respectively, prior to a bacterial regrowth that reached the plateau value of the growth control curve at 13 to 24 h versus 24 to 36 h and persisted despite repeated administration of both drugs . The surviving bacterial cells were quinolone-resistant mutants (2 to 128 times the MIC) that exhibited cross-resistance to unrelated antibiotics . Their antibiotic resistance probably resulted from the overproduction of different multidrug resistance efflux system(s) . C(max)/MIC and area under the concentration-time curve from 0 to 24 h (AUC(0-24))/MIC values were at least threefold higher for moxifloxacin than for ciprofloxacin . Moreover, integral parameters of ciprofloxacin and moxifloxacin, in particular the area under the killing and regrowth curve from 0 to 48 h (AUBC(0-48), 342.3 to 401.3 versus 295.2 to 378.7 h x log CFU/ml, respectively) and the area between the control growth curve and the killing and regrowth curve from 0 to 48 h (ABBC(0-48), 40.4 to 101.1 versus 72.9 to 144.7 h x log CFU/ml, respectively), demonstrated a better antibacterial effect of moxifloxacin than ciprofloxacin on S . maltophilia . However, selection of resistant mutants by both fluoroquinolones, although delayed with moxifloxacin, emphasizes the need to use maximal dosages and combined therapy in the treatment of systemic S . maltophilia infections. Anticancer Res, 2003 Nov-Dec, 23(6D), 5165 - 71 Colorectal adenomas produce lysozyme; Rubio CA; Lysozyme is an innate non-immunologic antibacterial enzyme produced by the Paneth cells of the upper intestinal tract . Lysozyme is not normally secreted in the lower intestinal tract . Previous reports indicate, however, that lysozyme may be secreted by colorectal neoplasias . The aim was to audit lysozyme expression in colorectal diseases including neoplasias . For that purpose, sections were stained with lysozyme (Muramidase), Ki67 (MIB1) and CD 68 . Intense lysozyme overexpression (+++) was compared among 177 colorectal tissues: 35 having normal mucosa, 20 regenerative mucosa in inflammatory bowel disease (IBD), 2 inflammatory polyps, 3 collagenous colitis, 2 melanosis coli, 21 hyperplastic polyps, 42 tubular adenomas, 9 serrated adenomas, 30 villous adenomas and 13 invasive carcinomas . Intense lysozyme overexpression (+++) was found in 9.5% of the hyperplastic polyps, in 97.6% of the tubular adenomas, in 88.9% of the serrated adenomas, in 93.3% of the villous adenomas, in 76.9% of the carcinomas, but in none of the other tissues investigated . Neoplastic colorectal cells may acquire the capacity to produce lysozyme . The presence of that enzyme may not be a haphazard, capricious event in mutated colorectal epithelial cells but part of a more elaborate molecular behavior, not necessarily antibacterial . Recently, it was demonstrated that patients having lysozyme-secreting breast carcinomas were associated with a favorable prognosis . Whether lysozyme expression has any bearing on the biological behavior of colorectal carcinomas remains to be elucidated . Lysozyme overexpression (+++) also occurred in 2 of the 21 hyperplastic polyps, suggesting that intense lysozyme production might herald a possible dysplastic evolution in some hyperplastic polyps. Am J Obstet Gynecol, 2004 Feb, 190(2), 448 - 55 Labor induces a maternal inflammatory response syndrome; Molloy EJ et al.; OBJECTIVE: We studied the effect of labor on maternal neutrophil phenotype . STUDY DESIGN: Neutrophil apoptosis with inflammatory cytokines and the expression of CD11b, CD34 and toll-like receptor 4 (TLR4) were assessed with flow cytometry in women at uncomplicated vaginal delivery (VD), and elective cesarean section (ElCS) without labor, emergency cesarean section with (EmCSL+) or without (EmCSL-) labor . RESULTS: Spontaneous neutrophil apoptosis is delayed in maternal neutrophils after VD, EmCSL+ or EmCSL- versus ElCS . In all groups lipopolysaccharide delayed apoptosis and increased CD11b expression . Elevated TLR4 expression in ElCS was associated with lipopolysaccharide responsiveness . CD34 was diminished in VD, indicating increased cell maturity . CONCLUSION: Normal labor primes the neutrophil and may enhance antibacterial function by inducing a mild maternal inflammatory response syndrome . Delayed neutrophil apoptosis may promote the neutrophilia seen in women after VD . We suggest that labor of any duration may be immunologically beneficial to the parturient. Bioorg Med Chem Lett, 2004 Mar 8, 14(5), 1273 - 7 Syntheses and biological evaluation of new fluoroquinolone antibacterials containing chiral oxiimino pyrrolidine; Choi DR et al.; The design and syntheses of new fluoroquinolone antibacterial agents having pyrrolidine ring at C-7 position are described . The pyrrolidine ring is optically active and possesses methyloxime functional group . Two of them have excellent in vitro antibacterial activities and pharmacokinetic profiles. Bioorg Med Chem Lett, 2004 Mar 8, 14(5), 1259 - 63 DNA binding ligands targeting drug-resistant Gram-positive bacteria . Part 2: C-terminal benzimidazoles and derivatives; Burli RW et al.; The synthesis and in vitro potency of DNA minor-groove binding antibacterials lacking the C-terminal amide bond are described . The crescent shaped molecules bear the positively charged amino group at an internal pyrrole unit instead of the C-terminus . Three structural parameters were investigated: the N-terminal unit, the internal amino group, and the C-terminal ring system . Several compounds demonstrated good in vitro potency against various Gram-positive bacteria and some molecules were moderately active against Escherichia coli, a representative Gram-negative strain. Bioorg Med Chem Lett, 2004 Mar 8, 14(5), 1085 - 7 Synthesis of stavudine amino acid ester prodrugs with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS; Sriram D et al.; A series of prodrugs of stavudine were synthesized in an effort to enhance spectrum of chemotherapeutic properties for the effective treatment of HIV/AIDS . The 5'-OH function of stavudine was esterified with ciprofloxacin, norfloxacin, isoniazide, pyrazinamide, piperazine and dimethylamine acetic acid . The anti-HIV-1 activity of the esters was determined in CEM cell line and stavudine ester bearing piperazine acetic acid was found to be the most potent compound with a selective index of >15,723 . Stavudine prodrug bearing ciprofloxacin and norfloxacin acetic acid showed 100% inhibition against Mycobacterium tuberculosis H(37)Rv at 6.25 microg/mL . The prodrugs also exhibited antibacterial activity against 24 pathogenic bacteria . In vitro hydrolysis of the various esters in human plasma indicated that these agents were relatively stable toward plasma esterases with t(1/2) ranging from 20-240 min. Am J Clin Dermatol, 2004, 5(1), 17 - 29 Disorders of keratinization: diagnosis and management; Shwayder T; Disorders of cornification are a group of diseases that share abnormalities in the manufacture or desquamation of corneocytes . This paper reviews the major and a few of the rarer ones with a concentration on their therapy . Ichthyosis vulgaris is probably a post-translational defect in pro-filaggrin expression . It shows fine white flaky scales of the extensor surfaces, trunk, flank, lower legs but spares the folds and wet areas . Treatment is with aggressive moisturization . Hydrocortisone creams may be needed to control itch . Recessive X-linked ichthyosis is due to a deficiency of cholesterol sulfatase . Boys with this condition show small dark scales around the ears, sides of the neck, extensor surfaces of the arms and legs, and the peri-umbilical region . It spares the folds and face . Treatment is with moisturizers, topical retinoid creams or with topical cholesterol-based creams . Checking for signs of contiguous gene disorders (Kallman or Conradi-Hunermann syndromes) is necessary . Bullous congenital ichthyosiform erythroderma is caused by mutations in keratins 1 and/or 10 . These patients are born as bright red babies with large blisters and erosions . Slowly, a porcupine quill-like waxy scaling develops . Blistering continues throughout life . Secondary infections of the skin cause pain, debility, and a very foul odor . Treatment is difficult . Topical moisturizers, descalers and retinoid creams help a little . Oral retinoids help a lot but can cause increased blistering . Controlling the odor is an ongoing issue using antibacterial washes, absorbing powders, and masking fragrances . Autosomal recessive ichthyosis is a term for both lamellar ichthyosis and congenital ishthysosiform erythroderma . They are caused by various mutations in transglutaminase-1 gene . In both instances patients are born as 'collodion babies' . Lamella ichthyosis has the very recognizable plate-like scale over the entire body . Children with congenital ishthysosiform erythroderma are red all over with a finer scale in some places and plate-like scales in others . Treatment is with topical moisturizers, retinoid creams, descalers, and in some cases oral retinoids . Palmar plantar keratodermas occur in conjunction with some ichthyoses, but also by themselves . Some are diffuse and others have discrete, corn-like hardenings . Treatment with topical acids, propylene glycol and retinoid creams help to some extent.Throughout the article pearls from my practice are included to assist the clinician in the day-to-day handling of these patients . A short section on genetic counseling concludes this article. J Med Food, 2003 Winter, 6(4), 401 - 3 Antibacterial activity of Aristolochia bracteata root extracts; Negi PS et al.; Aristolochia bracteata (Aristolochiaceae) is used in traditional medicines as a gastric stimulant and in the treatment of cancer, lung inflammation, and dysentery and snake bites . The present investigation was undertaken to evaluate the antibacterial activity of Aristolochia bracteata root extracts . Roots of A . bracteata were powdered and successively extracted with ethyl acetate, acetone, methanol, and water for 8 hours each using a Soxhlet extractor . Antibacterial activity of dried extracts was evaluated by the pour-plate method against a few Gram-positive and Gram-negative bacteria . All the crude extracts showed a broad spectrum of antibacterial activity . The ethyl acetate extract was found to be the most effective . This study shows the potential for replacement of synthetic preservatives by the use of natural extracts. J Endod, 2004 Feb, 30(2), 84 - 7 Antibacterial activity of 2% chlorhexidine gluconate and 5.25% sodium hypochlorite in infected root canal: in vivo study; Ercan E et al.; In this study, the antibacterial activity of the different antibacterial solutions using as root canal irrigant was compared in the teeth with pulpal necrosis and with periapical pathosis . Thirty root canals of incisors and premolars of 20 patients were used . Before and after the root canal preparation, two canal samples were obtained by a harvesting method using a sterile paper point in the first appointment . During the biomechanical preparation, both irrigant solutions were used for each tooth which were randomly divided into two groups . Last samples were also obtained before the root filling procedure . Samples obtained from the root canals were subjected to microbiologic processing, including anaerobic incubation on trypticase soy agar for 5 to 7 days . After counting of CFU on the plates, we concluded that both chlorhexidine gluconate and sodium hypochlorite were significantly effective to reduce the microorganisms in the teeth with necrotic pulp, periapical pathologies, or both, and could be used successfully as an irrigant solution. Eur J Pharmacol, 2004 Feb 20, 486(2), 189 - 200 In vivo experimental approach for the risk assessment of fluoroquinolone antibacterial agents-induced long QT syndrome; Chiba K et al.; The proarrhythmic effects of fluoroquinolone antibacterial agents, sitafloxacin, gatifloxacin and moxifloxacin, were compared using three in vivo models . In the halothane-anesthetized dogs (n=5), intravenous 10-min infusion of gatifloxacin and moxifloxacin (1-3 mg/kg) prolonged the ventricular effective refractory period and the repolarization period to a similar extent, whereas sitafloxacin (1-3 mg/kg) prolonged the former only . No significant change was detected in other cardiovascular parameters . In the chronic complete atrioventricular block dogs (n=4), oral administration of 100 mg/kg of gatifloxacin (2 of 4) and moxifloxacin (3 of 4) induced torsades de pointes, which was not observed by sitafloxacin . In the alpha-chloralose-anesthetized rabbits (n=5), intravenous 20-min infusion of 60 mg/kg of gatifloxacin induced torsades de pointes (1 of 5) in the presence of methoxamine infusion, which was not observed by sitafloxacin or moxifloxacin . Thus, the halothane-anesthetized model is suitable for assessing QT prolongation, whereas the chronic complete atrioventricular block model is sensitive for detecting torsadogenic action of drugs . The alpha-chloralose-anesthetized model is the simplest and least expensive method, but its sensitivity to detect proarrhythmic action may be less great. Crit Care, 2004 Feb, 8(1), R35 - 41 Epub 2003 Dec 23. Endotoxin neutralization and anti-inflammatory effects of tobramycin and ceftazidime in porcine endotoxin shock; Goscinski G et al.; INTRODUCTION: Antibiotics used for treatment of severe bacterial infections have been shown to exert effects on the inflammatory response in addition to their antibacterial effects . The aim of the present study was to investigate whether the biological effects of endotoxin in a porcine model could be neutralized by tobramycin, and whether tobramycin or ceftazidime was able to modulate the inflammatory response . METHOD: Thirteen piglets were subjected to endotoxin infusion at an initial rate of 4 microgram/kg per hour, which was reduced to 1 microgram/kg per hour after 30 min . Before endotoxin infusion, the animals received saline (n = 4), ceftazidime (n = 5), or tobramycin (n = 4) at clinically relevant doses . Physiological parameters were measured and blood samples were taken hourly for 6 hours for analysis of tumour necrosis factor-alpha, IL-6 and endotoxin concentrations . RESULTS: All of the animals exhibited physiological signs of severe sepsis without major differences between the groups . Plasma endotoxin concentration was stable after 1 hour . There were no differences in endotoxin concentration or initial tumour necrosis factor-alpha and IL-6 concentrations between the groups . At 6 hours the IL-6 concentration was significantly lower in the ceftazidime group than in the saline group (P < 0.05), and in both the ceftazidime and the tobramycin groups there were significantly greater reductions from peak values (P < 0.05) . CONCLUSION: There was no neutralization of the biological effects of endotoxin in this porcine model . However, our data indicate a possible anti-inflammatory effect exerted by both ceftazidime and tobramycin, which manifested as a significantly greater reduction in IL-6 in comparison with the untreated group. Clin Biochem, 2004 Mar, 37(3), 204 - 9 Circulating cytokines as markers of systemic inflammatory response in severe community-acquired pneumonia; Igonin AA et al.; OBJECTIVES: To assess the influence of empirical antibacterial therapy on systemic inflammatory response in patients with severe community-acquired pneumonia (CAP) . MATERIAL AND METHODS: Thirty consecutive patients with CAP meeting systemic inflammatory response syndrome (SIRS) criteria were recruited into this study . Blood samples for measurement of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and C-reactive protein (CRP) concentrations were drawn on days 1, 3, 5, 7 and 10 . For analysis, these patients were divided into two subgroups according to British Thoracic Society (BTS) severity score and to clinical response to the initial antibacterial therapy . RESULTS: In the group with severe CAP (n= 15), serum concentrations of IL-6 (P = 0.0001), IL-8, (P = 0.001), IL-10 (P = 0.0001) and CRP (P = 0.0001) were significantly higher compared to patients from the non-severe group (n= 15) . IL-6 presented with a sharp decrease between days 1 and 3 in non-responders with severe CAP (P = 0.004) . IL-6 concentrations on day 1 were significantly associated with a response to empirical antibacterial treatment by day 3 . CONCLUSION: Despite the absence of a clinical response to empirical antibacterial treatment as assessed by conventional clinical parameters on day 3 in patients with severe CAP meeting SIRS criteria, there was a marked reduction in the degree of the systemic inflammatory response as reflected by IL-6 levels. J Chromatogr A, 2004 Feb 20, 1027(1-2), 121 - 6 Capillary gas chromatography-mass spectrometry of volatile and semi-volatile compounds of Salvia officinalis; Radulescu V et al.; The essential oil and infusion of Salvia officinalis leaves have been widely applied in traditional medicine since ancient times and nowadays subjected to extensive research of their antibacterial, antiviral and cytotoxic properties . This paper shows chemical composition data of S . officinalis leaves essential oil isolated by steam distillation using a Clevenger-type apparatus . Also, the paper presents the chemical content of volatile and semi-volatile compounds of S . officinalis leaves infusion . The volatile and semi-volatile compounds of S . officinalis leaves infusion were isolated by solid-phase extraction (SPE) and liquid-liquid extraction with hexane and dichloromethane . SPE was carried out on 500 mg octadecylsilane (C18) cartridges and elution with dichloromethane . Liquid-liquid extraction was performed with hexane and dichloromethane . The essential oil in dichloromethane and infusion extracts in hexane and dichloromethane were analyzed by gas chromatography coupled with mass spectrometry . The quantitative results obtained by solid-phase extraction and liquid-liquid extraction showed that SPE on C18 performed the highest recovery of the volatile compounds from infusion sample. Boll Chim Farm, 2003 Nov, 142(9), 406 - 9 Synthesis of some new thiazole derivatives of pharmaceutical interest; el-Ablack FZ; Reaction of 4-amino-3-phenyl-5-ethoxycarbonyl-thiazole-2-thione with phenylisothiocyanate gave (2) which when boiled with acetic acid gave (3) . Treatment of (2) with monochloroacetic acid resulted in the formation of thiazolidinone derivative (4) . Reaction of (2) with malonic acid gave (5) . Condensation of (1) with aromatic aldehydes afforded Schiffe base derivatives (6a,b) . Treatment of (1) with malononitrile, ethyl cyanoacetate and acetonitrile resulted the formation of pyridine derivatives (7a,b,c) . The reaction of (1) with urea and thiourea gave compound (8) . Condensation of (1) with o-phenylenediamine and o-aminophenol gave compound (9) . Reaction of (1) with nitrous acid followed by coupling with ethylacetoacetate afforded (10) . Bromination of (10) gave bromo derivative (11) . The structures of the hitherto unknown compounds have been confirmed by analytical and spectral methods . The newly synthesized compounds were screened for antibacterial activity. Ann Periodontol, 2003 Dec, 8(1), 182 - 92 Microbial identification in the management of periodontal diseases . A systematic review; Listgarten MA et al.; BACKGROUND: Our understanding of the complexity of the oral microbiota continues to improve as new technologies, such as the analysis of 16S rRNA bacterial genes, are utilized . Despite the difficult of cataloguing all microorganisms and determining their pathogenic potential, some species, mostly members of the resident oral microbiota, have been identified as likely periodontal pathogens . However, for microbial diagnosis to be of value, it needs to affect disease diagnosis and/or treatment planning as well as result in superior treatment outcomes and/or provide an economic benefit to the patient . RATIONALE: The purposes of this systematic review were to determine if microbial identification influences periodontal patient management and whether treatment outcomes are better compared to patients whose treatment plans are developed without this information . FOCUSED QUESTION: In patients with periodontal diseases, does microbial identification influence patient management compared to treatment prescribed without this information? SEARCH PROTOCOL: The MEDLINE database was searched for clinical studies in English from 1991 through 2002 by 2 investigators . Hand searches were performed on the Journal of Clinical Periodontology, Journal of Periodontology, Journal of Periodontal Research, Oral Microbiology and Immunology, and Periodontology 2000 . In addition, directors of diagnostic laboratories were contacted about unpublished data . SELECTION CRITERIA: INCLUSION CRITERIA: Articles in which bacterial identification influenced patient treatment were preferred as were those reporting longitudinal data demonstrating a direct relationship between the presence or absence of certain bacteria and subsequent alterations in clinical variables . Because of the limited number of studies, all articles, including case reports, were considered . EXCLUSION CRITERIA: Review articles without original data were excluded, although references were examined for possible inclusion . Articles reporting data showing associations between certain microorganisms and disease or health that did not affect treatment were excluded . Clinical trials testing antibacterial agents for their ability to enhance mechanical debridement were not included since bacterial identification had little effect on drug selection or experimental group assignment . Articles dealing with implants rather than natural teeth were omitted . DATA ANALYSIS AND COLLECTION: The heterogeneity of the published data precludes any meaningful pooling of data or meta-analysis . The pertinent literature, including relevant variables of plaque, gingivitis, and bleeding on probing scores; probing depth; clinical attachment level; number of lost teeth; and microbial changes; and patient-centered outcomes including decrease in morbidity, reduced need for surgery, and duration and cost of treatment are summarized . MAIN RESULTS: 1 . There was a lack of articles with a high evidence rating; most pertinent articles were either case reports or case series without controls . 2 . Because reports were heterogeneous regarding study design, patient selection, and data collection, meta-analysis was not feasible and results are summarized in tabular format . 3 . This report is based on a total of 24 studies, representing a total patient population of approximately 835 . 4 . Thirteen studies reported on microbiological identification as an aid in treatment planning . 5 . Eleven studies reported a differential clinical response depending on the detection or lack of detection of specific organisms . REVIEWERS' CONCLUSIONS: 1 . The published material suggests that microbiological monitoring may be useful in management of selected patients who do not respond to standard therapy . 2 . Some practitioners consider microbial identification a valuable adjunct to managing patients with certain forms of periodontitis, although there is a lack of strong evidence to this effect . 3 . Additional research is needed to address this issue. Eur J Immunol, 2004 Jan, 34(1), 174 - 83 Pulmonary tuberculosis in BALB/c mice with non-functional IL-4 genes: changes in the inflammatory effects of TNF-alpha and in the regulation of fibrosis; Hernandez-Pando R et al.; In BALB/c mice, as in man, progressive pulmonary tuberculosis is accompanied by increasing expression of IL-4 . Therefore we have used BALB/c mice with disrupted IL-4 genes (IL-4(-/-)) to investigate the role of IL-4 in pulmonary tuberculosis, with particular emphasis on the toxicity of TNF-alpha and on fibrosis, both of which are neglected aspects of human tuberculosis . Delayed-type hypersensitivity (DTH) sites in IL-4(+/+) mice were sensitive to the toxicity of locally injected TNF-alpha, whereas DTH sites in IL-4(-/-) mice were not . However, intravenous administration of IL-4 to IL-4(-/-) mice restored the sensitivity of the DTH sites to pro-inflammatory effects of TNF-alpha . In late disease, the lungs of IL-4(+/+) mice expressed low IFN-gamma, but high TGF-beta and IL-4, correlating with fibrosis, detected as a high hydroxyproline content . In contrast, TGF-beta peaked 7 days after infection in the lungs of the IL-4(-/-) mice, and then fell to very low levels in the late disease, while IFN-gamma remained high . Accordingly, hydroxyproline content was reduced in infected IL-4(-/-) mice compared to IL-4(+/+) controls . In conclusion, the findings suggest that IL-4 has modestly detrimental effects on the antibacterial efficacy of the Th1 response, and larger effects on the toxicity of TNF-alpha, and on fibrosis. Mol Cell, 2004 Feb 13, 13(3), 307 - 16 Repair of DNA covalently linked to protein; Connelly JC et al.; A potentially lethal form of DNA/RNA modification, a cleavage complex, occurs when a nucleic acid-processing enzyme that acts via a transient covalent intermediate becomes trapped at its site of action . A number of overlapping pathways act to repair these lesions and many of the enzymes involved are those that catalyze recombinational-repair processes . A protein, Tdp1, has been identified that reverses cleavage-complex formation by specifically hydrolyzing a tyrosyl-DNA phosphodiester bond . The study of these pathways is both interesting and pertinent as they modulate the effectiveness of many antitumor/antibacterial drugs that act by stabilizing cleavage-complexes in vivo. Am J Physiol Lung Cell Mol Physiol, 2004 Jun, 286(6), L1302 - 10 Epub 2004 Feb 13. Roles for early response cytokines during Escherichia coli pneumonia revealed by mice with combined deficiencies of all signaling receptors for TNF and IL-1; Mizgerd JP et al.; During infection, inflammation is essential for host defense, but it can injure tissues and compromise organ function . TNF-alpha and IL-1 (alpha and beta) are early response cytokines that facilitate inflammation . To determine the roles of these cytokines with overlapping functions, we generated mice deficient in all of the three receptors mediating their effects (TNFR1, TNFR2, and IL-1RI) . During Escherichia coli pneumonia, receptor deficiency decreased neutrophil recruitment and edema accumulation to half of the levels observed in wild-type mice . Thus these receptors contributed to maximal responses, but substantial inflammation progressed independently of them . Receptor deficiency compromised antibacterial efficacy for some infectious doses . Decreased ventilation during E . coli pneumonia was not affected by receptor deficiency . However, the loss of lung compliance during pneumonia was substantially attenuated by receptor deficiency . Thus during E . coli pneumonia in mice, the lack of signaling from TNF-alpha and IL-1 decreases inflammation and preserves lung compliance. Mini Rev Med Chem, 2004 Feb, 4(2), 189 - 200 Antiviral sulfonamide derivatives; Supuran CT et al.; The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, diuretic, hypoglycemic, antithyroid and anticancer activity among others . A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial antiviral activity in vitro and in vivo . The review summarizes recent classes of sulfonamides and related sulfonyl derivatives disclosed as effective such agents . Thus, at least some HIV protease inhibitors used clinically (amprenavir) or compounds in advanced clinical trials (tipranavir, TMC-126, TMC-114, etc.) possess sulfonamide moieties in their molecules, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with less toxicity or activity against drug-resistant viruses . Several non nucleoside HIV reverse transcriptase or HIV integrase inhibitors containing sulfonamide groups were also reported . Another approach to inhibit the growth of retroviruses, including HIV, targets the ejection of zinc ions from critical zinc finger viral proteins, which has as a consequence the inhibition of viral replication in the absence of mutations leading to drug resistance phenotypes . Most compounds with antiviral activity possessing this mechanism of action incorporate in their molecules primary sulfonamide groups . Finally, some small molecule chemokine antagonists acting as HIV entry inhibitors also possess sulfonamide functionalities in their scaffold. Org Lett, 2004 Feb 19, 6(4), 557 - 60 Biocidal activity of polystyrenes that are cationic by virtue of protonation; Gelman MA et al.; {structure: see text} Poly(1) kills bacteria (Gram-positive and -negative) and lyses human erythrocytes; this biocidal profile is similar to that of the peptide toxin mellitin . Poly(1) has antibacterial activity comparable to that of a potent derivative of the host defense peptide magainin II, but lacks magainin's selectivity for bacteria over erythrocytes . An analogous N-quaternized polymer, poly(3), is less biocidal than poly(1), suggesting that reversible N-protonation leads to greater biocidal activity than does irreversible N-quaternization. Food Chem Toxicol, 2004 Mar, 42(3), 389 - 95 Peri- and postnatal developmental toxicity of the fluoroquinolone antibacterial DW-116 in rats; Kim JC et al.; DW-116 is a fluoroquinolone antibacterial developed by Dong-Wha Pharmaceutical Industry Co . The aim of this study is to determine the potential adverse effects of this chemical on pregnancy, delivery and lactation of dams and on peri- and postnatal development of F1 offspring . The test chemical was orally administered to pregnant rats from day 16 of pregnancy, through parturition and throughout the period of lactation up to weaning (postnatal day 21) at dose levels of 0, 10, 50, or 250 mg/kg/day . The progeny were examined at birth and subsequently to weaning . Mortality, body weight change, physical signs of postnatal development (pinna detachment, incisor eruption, fur development, eye opening, testis descent and vaginal opening) and behavioral function (righting reflex, negative geotaxis, grip-strength, pupillary reflex, acoustic startle response, rotating rod test, open field test and water-filled T-maze test) were evaluated . When the exposed offspring reached maturity (11 weeks old) their reproductive capacity was assessed . Maternal toxicity was observed only in the highest dose group and was limited to decreased food consumption during the late stage of pregnancy . However, this change was not observed during the lactation period . There were no adverse effects on mortality, clinical signs, body weight, necropsy findings, organ weight of dams in any treatment group . No adverse effects on the offspring were seen with the low and middle doses tested, but the highest dose increased postnatal mortality . The number of stillborn was also increased at the highest dose but the difference was not statistically significant . Meanwhile, no treatment-related effects were observed in clinical sign, developmental and behavioral landmarks and necropsy findings at any dose levels tested . There were no treatment-related effects on the mating of the F1 generation and resulting F2 offspring . The results of this study indicate that the peri- and postnatal administration of DW-116 to female rats results in an increase in postnatal mortality at a minimally maternotoxic dose, i.e., 250 mg/kg/day . Under the experimental conditions, the no-observed-adverse-effect level for peri- and postnatal developmental toxicity was considered to be 50 mg/kg/day. Int Endod J, 2004 Feb, 37(2), 132 - 8 Endodontic treatment of primary teeth using a combination of antibacterial drugs; Takushige T et al.; AIM: To evaluate the clinical outcome of 'Lesion Sterilization and Tissue Repair' (LSTR) therapy for endodontic treatment of primary teeth . METHODOLOGY: A mixture of metronidazole, ciprofloxacin, and minocycline (3Mix) in ointment (macrogol mixed with propylene glycol: MP) or in a root canal sealer was used to disinfect infected root canals of 56 patients aged 4-18 years . Out of a total of 87 primary teeth, 81 cases had physiologic root resorption . A total of 54 radiolucent periradicular lesions were present . The root canals were not prepared before or after disinfection . 3Mix medicament (3Mix-MP/3Mix-sealer) was placed at orifices of root canals or on the bottom of pulp chambers, and then sealed with glass-ionomer cement and further reinforced by a composite resin inlay prepared using a direct method and cemented with resin . RESULTS: In all cases, clinical symptoms such as gingival swelling (52 cases), sinus tracts (22 cases), induced dull pain (3 cases), spontaneous dull pain (26 cases), and pain on biting (46 cases) disappeared after treatment, although in four cases clinical signs and symptoms were finally resolved only after retreatment using the same procedures . Thus, gingival abscesses and fistulae, if present, disappeared after a few days . Successor permanent teeth erupted without any disorders, or were found radiographically to be normal and in the process of eruption . All the cases were evaluated as successful . The mean function time of the primary teeth was 680 days (range: 68-2390 days), except for one case in which the successor permanent tooth was congenitally missing . CONCLUSION: Primary teeth with periradicular lesions with or without physiologic root resorption were treated successfully by the LSTR endodontic therapy. J Gastroenterol, 2004 Jan, 39(1), 61 - 3 Inhibitory effect of green tea catechins in combination with sucralfate on Helicobacter pylori infection in Mongolian gerbils; Takabayashi F et al.; BACKGROUND: The occurrence of antibiotic-resistant Helicobacter pylori has been reported . It is desirable to develop an effective method to prevent the occurrence of resistant strains of Helicobacter pylori . Green tea catechins (GTCs) have been reported to have an antibacterial effect . Therefore, the possibility of eradicating Helicobacter pylori by the oral administration of GTCs was investigated . METHODS: Solutions of GTCs and solutions of GTCs adsorbed to sucralfate (GTC-scf), at concentrations of 20 mg GTCs and/or 20 mg sucralfate/ml were prepared . Then 1 ml of the GTC-scf or the GTC solution was administered daily, for 10 days to Mongolian gerbils infected with Helicobacter pylori . Then the stomachs were extirpated and homogenized . The homogenate was spread on selective medium plates . After 5-day culture, colony-forming units (CFU) of Helicobacter pylori were counted . RESULTS: The CFU of Helicobacter pylori was significantly decreased by GTC-scf . CONCLUSIONS: GTC-scf may have a bactericidal effect on Helicobacter pylori infection. Med Trop (Mars), 2003, 63(4-5), 491 - 7 {Antiparasitic treatments in pregnant women and in children in 2003}; Richard-Lenoble D et al.; Like antibacterial agents, antiparasite drugs for pregnant women and children must be chosen in function of the stage of pregnancy, age of the child, and expected benefit-risk ratio . While no agent is totally safe, there are few absolute contraindications . Most zones of serious endemic parasite disease are located in developing countries where parasite, bacterial, or viral conditions combined with poor nutrition treatment make it necessary to treat disease in a complex pathogenic environment that weakens pregnant women and children with multiple parasite infections . In both temperate and tropical zones, there have been few real therapeutic advances involving release of new products on the market or development of new indications for existing products . Constant appearance and extension of hematozoa resistance to conventional and even more recent antimalarial agents have prompted research to find new active drugs and long-lasting treatment combinations . Real therapeutic breakthroughs have resulted from the need to develop safe drugs without substantial side-effects for single-dose use in control programs against endemic parasite diseases in mass populations including pregnant women and young children in tropical zones . There are several notable examples in the field of major verminous diseases . Ivermectin is a versatile drug that can be used against filariasis as well as for management of intestinal worms or ectoparasitosis in temperate and tropical countries . Praziquantel is an important advance in platyhelminthiasis, especially bilharziais . Triclabendazole, the latest addition to the benzimidazole family, has shown promise as a substitute for bithionol, that is difficult to procure and not recommended in pregnant women, for treatment distomiasis occurring in pregnant women and children . Other examples include albendazole against giardiasis, nitazoxamide against cryptosporidiosis, artemisinine against bilharziasis, and paramomycine, not recommended in pregnant women, against leishmaniasis. Chem Pharm Bull (Tokyo), 2004 Feb, 52(2), 178 - 85 Synthesis, anticancer and antibacterial activity of some novel mononuclear Ru(II) complexes; Mazumder UK et al.; In search of potential anticancer drug candidates in ruthenium complexes, a series of mononuclear ruthenium complexes of the type {Ru(phen)(2)(nmit)}Cl(2) (Ru1), {Ru(bpy)(2)(nmit)}Cl(2) (Ru2), {Ru(phen)(2)(icpl)}Cl(2) (Ru3), Ru(bpy)(2)(icpl)}Cl(2) (Ru4) (phen=1,10-phenanthroline; bpy=2,2'-bipyridine; nmit=N-methyl-isatin-3-thiosemicarbazone, icpl=isatin-3-(4-Cl-phenyl)thiosemicarbazone) and {Ru(phen)(2)(aze)}Cl(2) (Ru5), {Ru(bpy)(2)(aze)}Cl(2) (Ru6) (aze=acetazolamide) and {Ru(phen)(2)(R-tsc)}(ClO(4))(2) (R=methyl (Ru7), ethyl (Ru8), cyclohexyl (Ru9), 4-Cl-phenyl (10), 4-Br-phenyl (Ru11), and 4-EtO-phenyl (Ru12), tsc=thiosemicarbazone) were prepared and characterized by elemental analysis, FTIR, (1)H-NMR and FAB-MS . Effect of these complexes on the growth of a transplantable murine tumor cell line (Ehrlich Ascites Carcinoma) and their antibacterial activity were studied . In cancer study the effect of hematological profile of the tumor hosts have also been studied . In the cancer study, the complexes Ru1-Ru4, Ru10 and Ru11 have remarkably decreased the tumor volume and viable ascitic cell count as indicated by trypan blue dye exclusion test (p<0.05) . Treatment with the ruthenium complexes prolonged the lifespan of Ehrlich Ascites Carcinoma (EAC) bearing mice . Tumor inhibition by the ruthenium chelates was followed by improvements in hemoglobin, RBC and WBC values . All the complexes showed antibacterial activity, except Ru5 and Ru6 . Thus, the results suggest that these ruthenium complexes have significant antitumor property and antibacterial activity . The results also reflect that the drug does not adversely affect the hematological profiles as compared to that of cisplatin on the host. Rev Med Chir Soc Med Nat Iasi, 2003 Oct-Dec, 107(4), 737 - 42 {Drug residues in food of animal origin}; Gavat V et al.; This paper reviews literature data on the stability of drug residues in food of animal origin . It was investigated the most important antibacterial, antihelminthic and sedative drugs and growth promoters used in food/producing animal treatments . The effects of storage (at -20 degrees C, 4 degrees C and temperature room) and a range of cooking processes (boiling, frying, roasting, grilling, microwaving) on residues was studied . The results are summarized in tables and showed that degradation and biological activity were varied between 0 and 100%. Postgrad Med, 2004 Jan, 115(1), 13 - 9 Acute sinusitis . When--and when not--to prescribe antibiotics; Leggett JE; Clinical diagnosis of acute sinusitis is troublesome because it involves use of a cluster of diagnostic criteria that have only moderate s